1、wangyuting MDDepartment of Infectious Diseases,Childrens Hospital of Chongqing Medical University Tuberculosis in childrenEPIDEMIOLOGY-TBnTuberculosis is an infectious disease caused by Mycobacterium tuberculosis.nTB has affected human for a long time.nNow,TB remains a leading public health problem.
2、Characteristics of pediatric TB1.More severe tuberculosis infection2.Tissues and organs are hypersensitivity to tuberculosis bacili 3.Lymphatic system involved widely4.Systemic spread tendency 5.the location of primary focus in lungs is special6.prognosis is good in most children with primary tuberc
3、ulosis and lesion is healed with absorption,calcification or scleroma7.Most of them have contact history with tuberculosis patients8.The smaller the age,the bigger the PPD-test valuePrimary pulmonary tuberculosislPrimary pulmonary TB is a tuberculosis that is caused by primary pulmonary infection of
4、 M.tuberculosis.lPrimary pulmonary TB includes:Primary complexTuberculosis of trachebronchial lymphnodes Droplet nuclei inhalationalveoliIngestion by PAMSIntracellular replication of bacilliDestruction of bacillidestruction of PAMSTubercle formationLymphogenic spreadHilar lymph nodesPrimary focuslym
5、phangitislymphadenitisPrimary complexPathogenesisPAM:pulmonary alveolar macrophages typicalTuberculosis of trachebronchial lymphnodesPrimary palmonary tuberculosisatypicalprimary complexLymphadenitisPrimary focusLymphangitisPathologypLocation of primary focus:l low zones of lobus superior pulmonis o
6、r upper zone of lobus inferior pulmonisl subpleurall right lung mostlypBasic lesions：pepithelioid cells,lymphocytes,and fibroblasts l caseous necrosis1.Tuberculosis toxic symptomsLow fever,night sweats,anorexia,weight loss,and fatigue 2.Lung clinical manifestatios：Symptoms is mild:dry coughSigns are
7、 not obvious generally(signs in lung is not consistent with the lesions in lung lesions not consistent)Clinical manifestations 3.Oppression symptoms of Bronchial lymph node4.Extrapulmonary clinical manifestations：5.others：Clinical manifestations Deterioration:Hematogenic spreadHealing with u obsorpt
8、ionu calcificationu scleromaProgression Expansion of lesionsPrimary complexPrognosis of primary palmonary tuberculosis:Diagnosis 1.Epidemiology history：History of contact with tuberculosis personBCG vaccination historyHistory of infectious diseases recently2.Clinical manifestations：Tuberculosis toxi
9、c symptomsRespiratory symptoms Manifestations of tuberculosis hypersensitivity Diagnosis 3.auxiliary examination(1)PPD testStrong positivePPD test result is from negative to positive PPD test result is positive in 3 years old children uninoculated BCGsuggest active tuberculosis in body 3.auxiliary e
10、xamination(2)Chest X-ray radiograph:the main diagnostic basis3.auxiliary examination(3)CT scan(4)Flexible bronchofiberscope examination(5)Finding tubercle bacillus in sputum or gastric aspirates(6)ESR(7)Antibody of TBTreatment 1.Antitubercular treatment (1)Principles：early treatment,appropriate dose
11、s,drug combination,standard medication,adhere to full course of treatment,two phases (2)Treatment regimen Active primary pulmonary tuberculosis INH +RFP +PZA or+SM/EMB Intensive treatment phase:3m 3m 3m 3mConsolidate treatment phase:6-9m 3-6m 0-3mTotal treatment 9-12m 6-9m 3-6m 3m儿童时期结核病的特点儿童时期结核病的特
12、点(重点重点、掌握）、掌握）原发型肺结核病理（原发型肺结核病理（熟悉熟悉、了解）、了解）发病机理（了解）发病机理（了解）临床表现（临床表现（重点重点、掌握）、掌握）诊断（诊断（重点重点、掌握）、掌握）转归转归（重点重点、掌握）、掌握）治疗（治疗（熟悉熟悉、掌握方案及总疗程掌握方案及总疗程）Summary:Tuberculous MeningitisWangyuting MDTuberculous meningitis(TBM)nTuberculous meningitis is the most serious TB and is uniformly fatal without treatme
13、ntnTBM is 2540%of all types of TB in childrennThe younger the children,the more common to develop TBM.60%of TBM in Children is under 3 years old and it is always a part of systemic disseminated tuberculosis.nTBM often occurs within 1 year of initial infection,especially in the first 26 months of inf
14、ection.nHigh rates of sequelae and high case-fatality(15-30%)Tubercle BacilliPrimary ComplexTuberculous MeningitisLung,CNS,liver,spleen,bone,ect Miliary TBPrimary Complex deteriorationFormation Rich foci in Meninges&brain parenchymaRupture into subarachnoid space Immuno-compromised:such as measles,p
15、ertussis in distant future forceacute generalized hematogenic spreadoccult hematogenic spreadPATHOPHYSIOLOGY 1.Brief DescriptionsnChronic meningitis.ncharacterized as a meningoencephalitisPATHOLOGYA.Leptomeningesndiffuse hyperemianedemaninflammatory exudatesntubercles(Rich focus):discrete and white
16、granules scattered over the leptomeninges ncaseous necrosis 2.Gross FindingsPATHOLOGYB.Subarachnoid SpacenThere are inflammatory exudates in subarachnoid spaces,particularly over the ventral surface of the brain stem(at the base of the brain),obliterating arteries and encasing cranial nerves(VII,III
17、,VI,etc.).-Basal meningitis2.Gross FindingsPATHOLOGYC.brain parenchymaTubercle,tuberculoma,and caseous necrosisPATHOLOGY2.Gross Findings3.Micro FindingsPATHOLOGIC EFFECTSnThree general processes produce the subsequent neurological pathology:adhesion formation obliterative vasculitis encephalitis1.Ad
18、hesions formation -Cranial nerve palsynBasal meningitis,there are adhesions around the interpeduncular fossa and related structures,can compromise cranial nerves.nCranial nerves can be compromised,particularly CN III(Oculomotor nerve)CN VI(abducens nerve)CN VII(Facial nerve)PATHOLOGIC EFFECTS1.Adhes
19、ions formation -HydrocephalusPATHOLOGIC EFFECTS1.Adhesions formation -HydrocephalusHyperemia of choroids overproduction of CSF Inflammatory adherence of Arachnoid granulations defective absorption of CSF Communicating hydrocephalus The route of CSF flow is obstructedObstructive hydrocephalusAtrophyP
20、ATHOLOGIC EFFECTSanterior cerebral artery arteria cerebri media posterior communicating arterybasal artery vertebral artery cervical internal carotid artery pontine arteries 2.Obliterative vasculitisPATHOLOGIC EFFECTSnExudates,vasculitis,and hydrocephalus each exert their own effect on brain parench
21、yma and cause encephalitis in TBM.nThe intensity of the basal inflammatory process extends into the parenchyma resulting in encephalitis 3.Encephalitis PATHOLOGIC EFFECTS exudatesadhesion formation obliterative vasculitisencephalitisedema intracranial hypertensionPATHOLOGIC EFFECTS4.Edema A.Stage 1(
22、Prodrome stage)1-2 weeks1.Tuberculous toxic symptoms:ulow to moderate grade fever,fatigue,malaise,anorexia,loss of weight,night sweat2.Mental status changes:alternant of irritability and drowsiness3.Headache,vomiting 4.Focal neurologic signs are absent5.CSF is abnormal CLINICAL MANIFESTIONSB.Stage 2
23、(Meningeal Irritation Stage)1-2 weeks1.More serious TB toxic symptoms 2.Neurologcal symptoms and signs:(1)Meningeal Irritation:nuchal rigidity,Kernig sign or Brudzinski sign (2)Intracranial hypertension:usevere headache,irritation,projectile vomiting,seizures,etc (3)Altered consciousness:such as let
24、hargy (4)Cranial neuropathies:palsy of cranial nerve 3,6,7,etc.(5)Minor focal neurological deficits:umonoplegia,hemiplegia,aphasia,hemiparesis,tetraparesis,etc.Cranial nerve III palsy Cranial nerve VII palsyCLINICAL MANIFESTIONSC.Stage 3(Coma Stage)1-3 weeks1.Depletion:extremely maransis2.Neurologic
25、al symptoms and signs are more sever (1)progressive altered state of consciousness:coma,decerebrate rigidity (2)frequent convulsion (3)hyponatraemia due to inappropriate ADH secretion by hypophysis (4)severe focal neurological deficits:hemiplegia or paraplegia (5)deterioration in vital signs and dea
26、d from cerebral hernia eventuallyCLINICAL MANIFESTIONSThe whole process lasts for 34 weeksCLINICAL MANIFESTIONSCharacteristics of TBM in infants and young children1.A rapid onset with abruptly high fever or convulsion2.The progression is rapid3.Atypical meningeal irritation4.Intracranial hypertensio
27、n manifests as bulging of anterior fontanelle and widening of cranial sutures in infant CLINICAL MANIFESTIONS 1.Cerebrospinal FluidINVESTIGATIONS-Lab Studies2.Tuberculin Skin Test 3.CT/MRI,Chest radiograph DIAGNOSIS nDiagnosis of TBV is made based on TB toxic symptoms,neurological symptoms and signs
28、,CSF findings Neuroimaging characteristicsnEvidence of extra-neural TB with appropriate microbiological,radiological or histopathological findings will add to the confirmation of the diagnosis.nA history of recent TB contact is also an important supporting feature of tuberculous etiology.nA definiti
29、ve diagnosis of TB etiology depends upon detection of Tubercle bacilli in CSF either by microscopy or in culture.DIFFERENTIAL DIAGNOSISnPyogenic meningitisnViral meningoencephalitisnCryptococcal meningitisTREATMENT1.Supportive and Symptomatic treatmentnBed rest and keep away from patients with pulmo
30、nary tuberculosis nNutritional support are paramount nKeep good hygiene for the coma children to prevent secondary infections,help them to change position frequently to prevent decubitinManagement of electrolyte abnormalities nAntipyreticsnControl of seizures:Diazepam(Valium)TREATMENT2.Anti-tubercul
31、ar treatmentA.Intensification phase of treatment:3 months INH,RFP,PZA,SM/EMBB.Continuation phase of treatment:912months INH,RFP or EMB In order to eliminate tubercle bacilli completely and prevent relapse in the host (I3R3P3E3 or I3R3P3S3)+I912R36The total course is 1 year at leastPay close attentio
32、n to the side effects TREATMENT 3.Management of intracranial hypertensionElevated intracranial pressure can be life-threateningnDehydrant:Mannitol(MNT)nDiuretic agent:furosemide4.Management of hydrocephalus Hydrocephalus is a common complication that may lead to permanent neurological damage or deat
33、h if left untreatednDiuretic agent:acetazolamide nVentriculoperitoneal shunt:to establish a communication between the CSF and a drainage cavity TREATMENTTREATMENT5.CorticosteriodsnMore effective used in early stage nChildren should be treated for 8-12 weeks nPay attention to the side effects of cort
34、icosteroidsCriteria for RecoveryFollow-up visit nClinical manifestations disappearnCSF examination is normal for at least 6 monthsnNo relapse within 2 years after completion of anti-tubercular treatmentPROGNOSISlThe clinical stage of diagnosis and treatmentlAge:infants or younger children are genera
35、lly worse than that of older childrenlDrug resistant strain lVariation of host immunitylAppropriate therapeutic regimen and completion the anti-tubercular agent regimenSummary:l 发病机理（了解）发病机理（了解）l 病理（了解）病理（了解）l 临床表现（临床表现（重点重点、掌握）、掌握）l 辅助检查（辅助检查（重点重点、掌握）、掌握）l 诊断（诊断（重点重点、掌握）、掌握）l 鉴别诊断（鉴别诊断（熟悉熟悉）l 治疗（治疗（重点重点、掌握方案及总疗程）、掌握方案及总疗程）l 预后（了解）预后（了解）l 治愈标准（治愈标准（熟悉熟悉）
